Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have suggested that some of the central nervous system (CNS) effects of interleukin-2 (IL-2) and perhaps other cytokines might be mediated through disruption of the blood-brain barrier (BBB). We investigated the ability of human IL-2 and, in selected studies, human IL-1 alpha and human IL-1 beta to disrupt the BBB to radioiodinated bovine serum albumin (RISA) after intravenous (i.v.) and intracerebroventricular (i.c.v.) injection. No disruption of the BBB occurred for up to 2 h after the i.v. injection of 2 micrograms/mouse of IL-2 (10(5) U/kg of body weight), 2 micrograms of IL-1 alpha (10(7) U/kg), or 2 micrograms of IL-1 beta (10(7) U/kg). This dose of i.v. IL-2 also did not affect BBB permeability to RISA in the brain to blood direction. Damage to the BBB induced by hypertension elicited by i.v. epinephrine was not enhanced or prolonged by IL-2. When given directly into the CNS by the i.c.v. route, 100 ng of IL-2 (2.2 x 10(5) U/kg of brain), 100 ng of IL-1 alpha (2.2 x 10(7) U/kg of brain), or 100 ng of IL-1 beta (2.2 x 10(7) U/kg of brain) had no effect on BBB integrity in either the blood to brain or the brain to blood direction. We conclude that the effects of IL-1 alpha, IL-1 beta, and IL-2 on the CNS, as studied under these conditions, are not due to disruption of the BBB but are mediated by other mechanisms including the ability of some interleukins to cross the BBB by a saturable transport system described previously.
 ...
PMID:The interleukins-1 alpha, -1 beta, and -2 do not acutely disrupt the murine blood-brain barrier. 152 30

The administration of recombinant human interleukin-1 beta (rhIL-1 beta) stimulates pluripotent cell growth and reduces mortality from infection in animal models. In this phase I trial, rhIL-1 beta (0.02-0.50 microgram/kg) was administered by 30-minute intravenous infusion once daily for 2 or 5 consecutive days. The dose was escalated with the subsequent cycle in the same patient if no hematologic response was observed. Nineteen patients with severe bone marrow failure received 60 courses of IL-1 beta. Diagnoses included autologous bone marrow transplant (BMT) (n = 5), allogeneic BMT (n = 7) or idiopathic aplastic anemia (n = 6) and 1 patient with chronic myeloid leukemia. Toxicities included fever (89%), chills (85%), hypertension (89%), hypotension (57%) and headache (95%). No complications were life-threatening and all either spontaneously resolved or were managed pharmacologically. In 8 of 19 patients there was an acute, transient increase in neutrophil counts. In 2 patients there was a transient increase in platelet count; however, no durable, clinically significant effects on peripheral blood counts were observed. In conclusion, administration of rhIL-1 beta in this population of patients had limited efficacy and moderate toxicity.
 ...
PMID:Phase I study of recombinant human interleukin-1 beta (rhIL-1 beta) in patients with bone marrow failure. 785 32

Using cultured neonatal ventricular myocytes, we investigated whether nitric oxide (NO) directly influences myocyte growth. Treatment of myocytes with phenylephrine stimulated growth, as indicated by increases in atrial natriuretic factor, brain natriuretic peptide (BNP) mRNA and BNP secretion, activator protein 1 activity (activation of early-response genes), and total cellular protein content. NO was stimulated by treatment of myocytes with interleukin-1 beta (IL-1 beta) or was generated by the NO donor nitroglycerin, and its effects on total protein content and BNP secretion were measured. Treatment of cardiocytes with 3.4 nmol/L IL-1 beta for 24 hours stimulated NO (nitrite) production by threefold, which resulted from an increase in the inducible isoform of NO synthase mRNA. Dexamethasone inhibited IL-1 beta induction of nitrite production, whereas the protein kinase C inhibitor staurosporine had no effect. IL-1 beta had no effect on either basal or phenylephrine-stimulated protein content but inhibited phenylephrine-stimulated BNP secretion. Nitroglycerin (10(-7) to 10(-3) mol/L) dose-dependently increased NO production; however, only the highest dose (10(-3) mol/L) reduced basal and phenylephrine-stimulated total protein content and BNP secretion. cGMP, a second messenger of NO, had no effect on either basal or phenylephrine-stimulated BNP secretion or total protein content. In conclusion, our data indicate that BNP mRNA is stimulated by phenylephrine as shown previously for atrial natriuretic factor. Although both BNP and total protein content are increased by phenylephrine, these effects are not inhibited by NO. However, IL-1 beta inhibits phenylephrine-stimulated BNP secretion but not total protein content, suggesting that regulation of BNP secretion can be dissociated from total protein synthesis during myocyte growth.
Hypertension 1995 Mar
PMID:Effects of interleukin-1 beta and nitric oxide on cardiac myocytes. 787 68

We investigated the role of central corticotropin-releasing factor (CRF) in the development of cardiovascular and thermal responses induced by stress or by interleukin-1 beta (IL-1 beta) in free-moving rats. Intracerebroventricular (icv) injection of alpha-helical CRF9-41 (10 micrograms), a CRF receptor antagonist, significantly attenuated hypertension, tachycardia, and a rise in body temperature induced by cage-switch stress, a mild stress. However, icv injection of alpha-helical CRF9-41 (10 micrograms) had no effect on hypertension, tachycardia, or fever induced by intraperitoneal (ip) injection of IL-1 beta (2 micrograms/kg) or icv prostaglandin E2 (PGE2, 100 ng). In contrast, icv injection of alpha-helical CRF9-41 (10 micrograms) significantly attenuated hypertension, tachycardia, or fever induced by icv injection of IL-1 beta (20 ng). The present results suggest that central CRF has an important role in the development of the cage-switch stress-induced responses, but it does not seem to contribute to the hypertension, tachycardia, and fever induced by ip IL-1 beta or by central PGE2. However, it is possible that when IL-1 beta directly acts on the central nervous system, some of its actions are mediated by central CRF.
 ...
PMID:Effect of a central CRF antagonist on cardiovascular and thermoregulatory responses induced by stress or IL-1 beta. 823 54

Pentoxifylline (PTX) has recently been shown to modulate TNF-alpha production and to reduce the incidence and severity of all major complications after BMT, including mucositis, veno-occlusive disease, renal insufficiency, hypertension, and graft-versus-host disease. To analyze in detail the effect of PTX on immune complications after BMT, we investigated the immunomodulatory effect of PTX on immune responses in vitro. The continuous presence of PTX significantly reduced the proliferative response of PBMC to PHA stimulation and to alloantigens in a dose-dependent manner. Starting at concentrations of 100 micrograms/ml, PTX was able to inhibit and, at 1000 micrograms/ml, completely block mitogen-induced proliferation. Maximal inhibition of more than 90% (91 +/- 4%) was also observed at PTX concentrations of 1000 micrograms/ml in the mixed lymphocyte culture (MLR) and by addition on day 0. However, lower but still significant suppression (13 +/- 7%) was achieved at concentrations of 10 micrograms/ml PTX. The inhibitory capacity of PTX was increased by mAbs against TNF-alpha (34 +/- 5% additional suppression at 100 micrograms/ml PTX) and not reversed by the addition of rTNF-alpha. The effect of PTX on the generation of CTLs in vitro was studied in the cell-mediated lymphotoxicity assay. PTX (100 micrograms/ml) significantly inhibited (P = 0.0178) the in vitro generation of CTLs when PTX was added to the culture on day 0. PTX also showed profound modulatory properties in the NK assay, with a reduction of 23 +/- 3% in specific lysis at 10 micrograms/ml PTX and maximal reductions of 88 +/- 3% at 1000 micrograms/ml PTX. Immunomodulatory properties of PTX were not only associated with blockage of TNF-alpha, as shown by decreased mRNA expression and TNF-alpha values in the culture supernatants, but also with an impaired production of other cytokines and secondary messages such as IFN-gamma and neopterin. PTX treatment, however, did not affect IFN-alpha or IL-1 beta production, and IL-6 release was even increased. PTX, therefore, has profound immunomodulatory properties in vitro, which are associated with selective inhibition of cytokine release and can be enhanced by the addition of mAbs against TNF-alpha, but not reversed by the addition of rTNF-alpha.
 ...
PMID:Immune response modulation by pentoxifylline in vitro. 833 42

Accumulating evidence tends to demonstrate that inflammatory processes are responsible for neurological damage and sequelae in bacterial meningitis in children and infants. Massive liberation of bacterial cell wall components (Lipopolysaccharide, acid teichoic polymers) induce a cascade of reactions including the secretion of many cytokines (such as TNF alpha and IL-1 beta) and prostaglandins (such as PAF and PGE2) which in turn leads to the development of cerebral oedema, intracranial hypertension and cerebral blood flow reduction. Dexamethasone (DXM) is effective at the beginning of the inflammatory cascade and its utilisation in the meningitis experimental model in animals has shown significant reduction in the inflammatory response to bacterial meningitis. The first clinical studies using DXM as an adjunctive therapy to antibiotics have demonstrated its beneficial effect in terms of complications and long-term neurological sequelae in Haemophilus influenzae meningitis in children and infants. It seems that a similar effect can be obtained in meningococcal and pneumococcal meningitis. Little information is actually available concerning the use of DXM in penicillin-resistant pneumococcal meningitis. The rare reported cases of ceftriaxone failure with DXM as treatment of penicillin-resistant pneumococcal meningitis had a favorable outcome with the use of vancomycin.
 ...
PMID:[Role of dexamethasone in the treatment of purulent meningitis in infants and in children]. 839 88

The plasmid pMK16 containing-SV40 replicated origin defective gene was efficiently introduced into early-passage human umbilical vein endothelial cells (HUVEC) using positively charged liposomes. The resulting cell line acquired an almost infinite lifespan, was morphologically unchanged, expressed SV40-antigen, and coexpressed von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), angiotensin conversion enzyme (ACE), and endothelin converting enzyme (ECE). In addition, these are the first immortalized human endothelial cells, to our knowledge, that biosynthesized and secreted interleukins (IL-1 beta and IL-6) in both a constitutive and regulated fashion and endothelin-1 (ET-1), the most potent vasoactive peptide, which has been suggested to be implicated in the pathogenesis of hypertension. Interestingly enough, both of the immortalized cells and the early-passage HUVEC from which the immortalized cells were obtained biosynthesized and secreted the same levels of ET-1 suggesting full maintenance of its biosynthetic pathway including the presence of active ECE, which cleaves big endothelin-1 (big-ET-1) to ET-1 and regulation factors. Moreover, the immortalized cells retained the ability to express the functional specific amino acid Na(+)-independent system Y+ transporter, which mediates L-arginine transport into endothelial cells from which endothelium-derived relaxing factor (EDRF, nitric oxide) is formed via the action of nitric oxide-synthase. Obtaining these immortalized human endothelial cells without alteration of the differentiated characteristics constitutes a useful model: (a) to study ET-1 secretion, gene regulation, and human ECE, which may be an important therapeutic target in disease conditions in which ET-1 is to be implicated; (b) to study L-arginine transport, which is a key step in the formation of EDRF; (c) to study IL-1 beta and IL-6 secretions, and gene regulations; (d) to substitute large quantities of HUVEC; and, finally, (e) to reproduce, starting with different primary endothelial cells both from human and animal origin.
 ...
PMID:Establishment of permanent human endothelial cells achieved by transfection with SV40 large T antigen that retain typical phenotypical and functional characteristics. 883 14

The inducible nitric oxide synthase (iNOS) present in vascular smooth muscle cells (VSMC) may play a role in the generation of nitric oxide (NO) in the vascular wall, regulating blood vessel tone in normotension and hypertension. In this study the effect of interleukin (IL)-1 beta, a cytokine that induces iNOS, on NO generation (measured as nitrite), cyclic guanosine monophosphate (cGMP) generation, and steady-state abundance of iNOS mRNA were examined in VSMC from 3 week old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, during the period preceding the elevation of blood pressure. With cell density dependent variations in nitrite production eliminated, VSMC from SHR and WKY did not differ in NO generation except after prolonged incubation (30 h), when SHR cells produced less NO. However, cGMP concentrations associated with IL-1 beta stimulation were significantly smaller in SHR VSMC than in cells from WKY. IL-1 beta stimulation resulted in increased abundance of iNOS mRNA to the same extent in both WKY and SHR VSMC. Inhibitors of NOS, NG-monomethyl-L-arginine (L-NMMA) and N omega-nitro-L-arginine methyl ester (L-NAME), did not block the induction of iNOS mRNA, although nitrite production and cGMP generation were inhibited. The protein synthesis inhibitor cycloheximide and the RNA synthesis inhibitor actinomycin-D almost completely blocked the production of nitrite in cells from both strains of rats. Actinomycin-D completely blocked the induction of iNOS mRNA by IL-1 beta in cells from both strains of rats, whereas cycloheximide partially blocked its synthesis in WKY, but had no significant effect on IL-1 beta induced expression of iNOS mRNA in SHR VSMC. Thus, IL-1 beta controls iNOS gene expression at the transcriptional level, and an intermediate labile protein, whose synthesis is inhibited by cycloheximide, is required for IL-1 beta stimulated induction of iNOS mRNA transcription in WKY cells but not in SHR. We conclude that although iNOS is expressed to similar extent in VSMC of prehypertensive SHR and WKY and similar amounts of NO are initially generated, there are differences between the VSMC of SHR and WKY in the regulation of the transcription of iNOS mRNA, there is a lower sustained production of NO, and there is a reduced generation of cGMP in response to IL-1 beta stimulated NO production. These differences between VSMC from prehypertensive SHR and WKY may indicate a pathophysiological role of iNOS in early blood pressure elevation in SHR.
 ...
PMID:Inducible nitric oxide synthase in vascular smooth muscle cells from prehypertensive spontaneously hypertensive rats. 887 43

In the kidney, prostanoids play a role as vasoactive and immunomodulatory mediators. One of the main biosynthetic enzymes, the inducible cyclooxygenase-2 (EC 1.14.99.1, Cox-2), has been recognized as a target of glucocorticoids. Therefore, we investigated whether the physiologically active corticosteroid aldosterone in the kidney might also interfere with prostaglandin (PG) synthesis. In two cell types, an epithelial cell line of tubular origin (MDCK) and rat renal mesangial cells, PGE2, release, Cox activity and Cox mRNA expression were determined after stimulation with phorbol ester and IL-1 beta, respectively. An increase in PGE2 release and Cox activity was observed, which correlated with an increase in Cox-2 mRNA expression. In MDCK cells, both dexamethasone and aldosterone were equally effective, suppressing all parameters measured by approximately 60%. A similar effect of aldosterone was also seen in mesangial cells, whereas dexamethasone was far more potent (> 90% inhibition at 10(-6) M). Whole cell binding assays showed the same number of receptors for aldosterone in both cell types (approximately 70,000 receptors/cell) but more than ten times higher receptor numbers for dexamethasone in mesangial cells than in MDCK cells (90,000 vs. 6000 receptors/cell). Receptor affinities of the corticosteroids were comparable. Thus, interaction of the corticosteroids with their cognate receptors was not sufficient to explain their different potencies but indicated the involvement of more complex regulatory mechanisms. Pathophysiologically, inhibition of PGE2 synthesis by aldosterone may play a role in the induction of hypertension by high concentrations of aldosterone.
 ...
PMID:Interference of corticosteroids with prostaglandin E2 synthesis at the level of cyclooxygenase-2 mRNA expression in kidney cells. 893 52

Phaeochromocytomas have been shown to produce not only catecholamines but other neuropeptides and hormones, with a variety of clinical manifestations. We report a 70-year-old female patient with phaeochromocytoma exhibiting sustained hypertension, low-grade fever, thrombocytosis, and elevated levels of plasma fibrinogen and C-reactive protein. Serum interleukin (IL)-6 levels were significantly elevated, whereas serum IL-1 alpha and IL-1 beta were not detectable. After surgical removal of the tumour, hypertension and low-grade fever disappeared, and the laboratory finding including serum IL-6 concentrations became normal. Immunohistochemical study of the tumour showed positive staining for IL-6. Culture of the resected tumour revealed the production of large amounts of IL-6. It is suggested that IL-6 secreted by the tumour was responsible for some of the clinical manifestations in this patient.
 ...
PMID:Interleukin-6 secreting phaeochromocytoma associated with clinical markers of inflammation. 919 15


1 2 3 Next >>